Integrated Physiology Core C: Project Summary The Integrated Physiology Core is a multi-service resource that provides Center Investigators and their laboratories the tools and advice needed to establish and study mouse (including transgenic and knockout) and human (i.e. 3D organoid cultures) models of gastrointestinal disease. Since the inception of our Center, this Core has expanded its use by the Research Base and become a highly cost effective and efficient resource for histology, genotyping, and physiology services. This Core also provides the Research Base with the training and resources to utilize human intestinal stem cell technology for their studies. The use of human intestinal stem cell derived enteroids/colonoids has rapidly evolved and is becoming a premier model for the study of human GI physiology and pathophysiology. During the initial funding period, the Core was used by 46 Core Center investigators (>70% utilized multiple services), resulting in 65 published manuscripts, and has been used by 7 out of 11 funded P/F projects. The services offered include 1) Advice on establishing and maintaining mouse colonies, including how to breed onto uniform backgrounds; 2) Genotyping, which includes developing and optimizing primers; 3) Histological services, which include tissue fixation and processing, embedding, sectioning (including cryosectioning), histopathological staining (e.g. H&E, PAS, Sirius Red), and tissue archiving. A tissue bank of H&E slides of GI organs of the mouse models studied by our Research Base are made available for other Core members to use for preliminary studies; 4) Histopathology consultation by an expert pathologist for characterization of mouse GI disease models; 5) Metabolic cages are available for metabolic balance studies, including blood, urine, stool analysis; 6) Ussing chamber/voltage clamp technology for measuring active ion transport and tight junction permeability and permselectivity;7) Multiplex ELISA for simultaneous measurement of ~100 analytes (e.g. cytokines, chemokines, growth factors) from a small volume (<100?l) sample of serum, tissue, or culture media; as well as 8) Training in establishing, maintaining, and using mouse and human enteroids as well as provision of growth factor conditioned media necessary for long- term culture.